Rosebud, the sled from Citizen Kane and the Ark of the Covenant from Raiders of the Lost Ark are visible in the lab security warehouse.

At the beginning of the film, when Wayne first goes into Adam's room, the meowing Kit-Cat Clock (from Honey, I Shrunk the Kids) can be seen in the upper-left corner of the screen.

The film was, at first, not supposed to be a sequel to Honey, I Shrunk the Kids. Originally titled "Big Baby," it was about a young toddler who grew to giant size by a freak accident involving a growth ray and eventually terrorized Las Vegas in a non-violent, yet Godzillaesque way. Disney saw the possibilities of making this into a follow up to Honey, I Shrunk the Kids and rewrote the script to the movie. Whereas most of the characters from Big Baby were rewritten as characters from Honey, I Shrunk the Kids, there was no character that could take the place of Amy Szalinski, Wayne and Diane's eldest child and only daughter, portrayed by Amy O'Neill. Instead of excluding her character from the story, Amy makes a brief appearance in the beginning of the film, and it is explained that she is leaving for college.

Much of the the dialogue between Mr. Szalinski and little Adam, such as the bedtime story and feeding time, was improvised by Rick Moranis in response to whatever Daniel Shalikar and Joshua Shalikar, the twins who played Adam, happened to say.

The scene when Adam was about to put the car in his mouth and Nick said, "Adam, don't eat us", was a nod to Honey, I Shrunk the Kids in which Nick said, "Dad, don't eat me".

Adam Szalinski is played by twin brothers Joshua Shalikar and Daniel Shalikar. Most films and TV shows that involve small children typically cast older children (typically ages 3 and 4) that look younger than they really are, however the Shalikars were 2 years old during the film's production, the same age as the character they were playing was supposed to be, due to the fact that they were fairly easy to work with and took direction well. Dan was noted as being the more adventurous of the two, while Josh was more cautious.

The water amusement park featured in this movie, Wet 'n Wild Las Vegas, closed down in 2004.

Actor Alex Daniels portrayed Adam in his "blown-up" form (he is credited as "Uncle Yanosh"). Daniels wore a 40-pound, electronic-headed "Adam suit" for the role, and was coached on how to mimic the movements of a toddler. Once suited up on the set, Daniels had to magnify his movements so they would show through the costume's heavy, clumsy folds. Occasionally, the heat inside the outfit proved too much for its coolant system, a vest with ice water pumped through tubes, prompting crew members who noticed Daniels faltering to yell, 'Get Alex outta there!'